We plan the following studies: 1. The mechanism and control of ion transport systems with particular emphasis on a) the proton pump of mitochondria, b) the Ca2+ pump of sarcoplasmic reticulum and plasma membranes, c) the Na+K+ ATPase of the plasma membrane, and c) other ion channels such as the Ca2+ and Na+ channels of plasma membranes. The general approach is that of isolation of the responsible protein(s) and reconstitution in artificial liposomes. We hope to study in these purified systems the mechanisms by which ATP energy is utilized to facilitate active ion transport, and in the case of the mitochondrial proton pump how an ion gradient is utilized for the generation of ATP from Pi and ADP. 2. The role of ion pumps and other ATPases as suppliers of ADP and Pi required for the high aerobic glycolysis of tumor cells. We plan a) to pursue to explore and possibility that a virus associated ATPase (e.g. in Avian myeloblastosis virus) participates in the aerobic glycolysis. an enzyme similar to the virus enzyme has now been found in some tumor cells as well as in brain vesicle preparations. b) Most of our efforts will be extended to the elucidation of the protein kinase cascade which we have shown to be operative in the Ehrlich ascites tumor cells and responsible for the phosphorylation of a tyrosine residue of the Beta subunit of the Na+K+ ATPase. Among the goals are the characterization of each of the kinase and their control of cAMP and small molecular weight polypeptides. We also plan to explore all the protein substrates that are being phosphorylated by the various members of the protein kinase cascade. From these studies we hope to get a better understanding of the remarkable pleotropic expressions in morphology and function that are induced by a single gene product kinase during transformation of a cell by a Rous sarcoma virus.